The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Dr. Earle F Burgess presented the results of ENZADA, a single arm phase II trial evaluating the triplet combination of enzalutamide, docetaxel, and ADT for patients with metastatic castrate sensitive prostate cancer (mCSPC).
Over the last few years, triplet therapy combinations with ADT + docetaxel combined with either darolutamide or abiraterone have emerged as standard of care options for the management of patients with mCSPC, based on the results of ARASENS and PEACE-1 which have demonstrated overall survival (OS) benefits with these combinations.1,2 As such, evaluation of further combination strategies in this space are warranted. In the ENZADA trial, the authors hypothesized that the combination of enzalutamide plus ADT/docetaxel would improve the one-year PSA complete response (CR) rate, a surrogate of improved OS in prior studies, compared to historic “controls” of ADT + docetaxel in patients with newly diagnosed mCSPC.
The ENZADA trial (NCT03246347) is a single institution phase II study of mCSPC patients who received ADT, docetaxel (75 mg/m2 IV every 3 weeks for up to 6 cycles), and enzalutamide 160 mg daily until evidence of radiographic progression. The primary endpoint was the one-year PSA CR. Secondary endpoints included safety/toxicity, best PSA response, time-to-castration resistance, and OS. Patients were stratified by radiographic volume of disease by CHAARTED criteria. This study was designed with 90% power and a 1-sided alpha of 0.1 to show an improvement in the one-year CR from 25% to 45%, with rejection of the null hypothesis if 14 of 39 evaluable subjects achieved a one-year PSA CR.
Between September 2017 and August 2021, 40 subjects were enrolled, of whom 36 were evaluable for the primary endpoint of one-year PSA CR. The median follow-up was 42.6 months (data cut-off: September 2, 2022). Of these 40 patients, 30 (75%) had high volume disease, and 32 (80%) presented with de novo metastatic disease. The median age was 64.5 years. With regards to race/ethnicity, 65% identified as Caucasian and 35% as African American or Black. The median pre-treatment PSA level was 129.5 ng/ml.
The six cycles of docetaxel were completed in 68% of subjects (27/40) and 10% (4/40) required enzalutamide dose modifications. The primary outcome of one-year PSA CR was observed in 22/36 (61%) patients overall (p<0.001), with no significant differences by race/ethnicity:
- White patients: 13/23 (57%)
- African American patients: 9/13 (69%, p=0.50)
The two- and four-year freedom from castration resistance rates were 62.4% and 53.5%, respectively (median time-to-castration resistance was not reached). Eleven deaths occurred in the cohort (African American: 3/14; White: 8/26). The OS rates at two and four years were 83.2% and 63.1%, respectively (median OS was note reached). The two- and four-year OS rates by race/ethnicity were as follows:
- White patients: 82.4% and 50.9%, respectively
- African American patients: 85.7% and 78.6%, respectively (p=0.26)
Treatment-related Grade 3-5 adverse events occurred in 17/40 (42.5%) patients, including three episodes of febrile neutropenia.
Dr. Burgess concluded that triplet therapy with ADT + docetaxel + enzalutamide improved one-year PSA CR rates compared to historical controls with ADT + docetaxel. These results are consistent with the recent ARASENS and PEACE-1 studies and support the use of triplet therapy regimens combining ADT, docetaxel, and androgen receptor signaling inhibitors in newly diagnosed mCSPC patients. No significant differences in outcome by race were observed in ENZADA.
Presented by: Earle F Burgess, MD, Medical Oncology, Atrium Health, Charlotte, NC
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.
References:- Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142.
- Fizazi K, Foulon S, Carles J, Roubaud G, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): A multicentre, open-label, randomized, phase 3 study with a 2 x 2 factorial design. Lancet. 2022 Apr 30;399(10336):1695-1707.